In the in-vivo dog model described previously we have studied the role of the liver in the metabolism of glucagon and somatostatin, demonstrating that this organ is responsible for approximately 30% of the total metabolic clearance of both peptides. In the past year we have studied the effects of glucose and protein feeding on the hepatic extraction of pancreatic hormones, and the relationship of these changes to hepatic glucose handling. It was found that after glucose ingestion the hepatic delivery and extraction of insulin doubled simultaneously with a fall in hepatic glucose output and hepatic glucose uptake. These changes in hepatic glucose handling were restored to basal levels at the same time as hepatic insulin delivery and extraction reverted to baseline. A similar but inverse relationship for glucagon was found after oral glucose. In the next year we hope to study the hepatic metabolism of pancreatic polypeptide and the relationship of hepatic insulin and glucagon degradation and biologic activity to hepatic receptor binding.